(ChemotherapyAdvisor) – A novel short-course, bortezomib-based prophylaxis for graft-versus-host-disease (GVHD) in HLA-mismatched unrelated donor (MMUD) reduced intensity conditioning (RIC) hematopoietic stem-cell transplantation (HSCT) was safe and efficacious and offered “encouraging” survival results, according to a study in the Journal of Clinical Oncology online August 6.
“Importantly, bortezomib-based MMUD transplantation achieved clinical outcomes comparable to HLA-matched transplantation, along with enhancement of various immune reconstitution parameters,” noted John Koreth, MBBS, DPhil, Dana-Farber Cancer Institute, Boston, MA, and colleagues.
In the prospective phase 1/2 trial, 45 patients with hematologic malignancies undergoing MMUD RIC HSCT received bortezomib once daily on days 1, 4, and 7 following peripheral blood stem-cell infusion plus standard tacrolimus and methotrexate. Forty of the patients (89%) had 1-locus and 5 (11%) had 2-loci mismatches (HLA-A, -B, -C, -DRB1, or -DQB1); median follow-up was 36.5 months (range, 17.4 to 59.6 months).
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Cumulative incidence of grade 2 to 4 acute GVHD was 22% (95% CI, 11%–35%) at 180 days; chronic GVHD was 29% (95% CI, 16%–43%) at 2 years. Two-year cumulative incidence of nonrelapse mortality (NRM) was 11% (95% CI, 4%–22%) and relapse, 38% (95% CI, 24%–52%). At 2 years, progression-free survival was 51% (95% CI, 36%–64%) and overall survival, 64% (95% CI, 49%–76%).
“Bortezomib-treated HLA-mismatched patients experienced rates of NRM, acute and chronic GVHD, and survival similar to those of contemporaneous HLA-matched RIC HSCT at our Institution,” they reported. Bortezomib also enhanced immune recovery, including CD8+ T-cell and natural killer cell reconstitution.
An accompanying article noted that based on these data, “bortezomib-based strategies can potentially join post-transplant cyclophosphamide and antithymocyte globulin as an effective strategy to prevent acute and chronic GVHD in the HLA-mismatch setting without ex vivo TCD [T-cell depletion]. However, only a prospective comparative trial of all these approaches will clarify the relative benefits of one strategy over another.”
